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Comparative study of the structure and interaction of the pore helices of the hERG and Kv1.5 potassium channels in model membranes

Comparative study of the structure and interaction of the pore helices of the hERG and Kv1.5 potassium channels in model membranes
Comparative study of the structure and interaction of the pore helices of the hERG and Kv1.5 potassium channels in model membranes
The hERG channel is a voltage-gated potassium channel found in cardiomyocytes that contributes to the repolarization of the cell membrane following the cardiac action potential, an important step in the regulation of the cardiac cycle. The lipids surrounding K+ channels have been shown to play a key role in their regulation, with anionic lipids shown to alter gating properties. In this study, we investigate how anionic lipids interact with the pore helix of hERG and compare the results with those from Kv1.5, which possesses a pore helix more typical of K+ channels. Circular dichroism studies of the pore helix secondary structure reveal that the presence of the anionic lipid DMPS within the bilayer results in a slight unfolding of the pore helices from both hERG and Kv1.5, albeit to a lesser extent for Kv1.5. In the presence of anionic lipids, the two pore helices exhibit significantly different interactions with the lipid bilayer. We demonstrate that the pore helix from hERG causes significant perturbation to the order in lipid bicelles, which contrasts with only small changes observed for Kv1.5. These observations suggest that the atypical sequence of the pore helix of hERG may play a key role in determining how anionic lipids influence its gating.
0175-7571
Beaugrand, Maiwenn
d3a66d51-72a1-4820-a520-0764e41e312e
Arnold, Alexander
f4dc0184-547e-4775-99a9-15083657a171
Bourgault, Steve
aad311bd-550e-43e2-9116-e58112597e70
Williamson, Philip
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Marcotte, Isabelle
6908440c-f797-48ee-b109-cfa557552ff2
Beaugrand, Maiwenn
d3a66d51-72a1-4820-a520-0764e41e312e
Arnold, Alexander
f4dc0184-547e-4775-99a9-15083657a171
Bourgault, Steve
aad311bd-550e-43e2-9116-e58112597e70
Williamson, Philip
0b7715c6-b60e-4e95-a1b1-6afc8b9f372a
Marcotte, Isabelle
6908440c-f797-48ee-b109-cfa557552ff2

Beaugrand, Maiwenn, Arnold, Alexander, Bourgault, Steve, Williamson, Philip and Marcotte, Isabelle (2017) Comparative study of the structure and interaction of the pore helices of the hERG and Kv1.5 potassium channels in model membranes. European Biophysics Journal. (doi:10.1007/s00249-017-1201-2).

Record type: Article

Abstract

The hERG channel is a voltage-gated potassium channel found in cardiomyocytes that contributes to the repolarization of the cell membrane following the cardiac action potential, an important step in the regulation of the cardiac cycle. The lipids surrounding K+ channels have been shown to play a key role in their regulation, with anionic lipids shown to alter gating properties. In this study, we investigate how anionic lipids interact with the pore helix of hERG and compare the results with those from Kv1.5, which possesses a pore helix more typical of K+ channels. Circular dichroism studies of the pore helix secondary structure reveal that the presence of the anionic lipid DMPS within the bilayer results in a slight unfolding of the pore helices from both hERG and Kv1.5, albeit to a lesser extent for Kv1.5. In the presence of anionic lipids, the two pore helices exhibit significantly different interactions with the lipid bilayer. We demonstrate that the pore helix from hERG causes significant perturbation to the order in lipid bicelles, which contrasts with only small changes observed for Kv1.5. These observations suggest that the atypical sequence of the pore helix of hERG may play a key role in determining how anionic lipids influence its gating.

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Accepted/In Press date: 17 February 2017
e-pub ahead of print date: 17 March 2017
Published date: 17 March 2017
Organisations: Molecular and Cellular

Identifiers

Local EPrints ID: 406906
URI: http://eprints.soton.ac.uk/id/eprint/406906
ISSN: 0175-7571
PURE UUID: 415e768c-18db-4b3c-b461-ba15d4d54563
ORCID for Philip Williamson: ORCID iD orcid.org/0000-0002-0231-8640

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Date deposited: 28 Mar 2017 01:03
Last modified: 20 Jul 2019 05:15

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